Richard D. Palmiter, PhD

Investigator at the Howard Hughes Medical Institute at University of Washington

Dr. Palmiter is known for his contributions to four different areas of molecular biology and animal physiology. His career began with a molecular dissection of the mechanisms by which steroid hormones regulate gene transcription. In the 1970's, he and his colleagues showed that sex steroids regulate the transcription of genes responsible for egg white production by laying hens.
Later his group turned their attention to the regulation and function of metallothionein genes. These gene products bind heavy metals such as zinc and copper and are thought to play roles in metal homeostasis and protection against metal toxicity and oxidative damage. Dr. Palmiter's group was the first to clone metallothionein genes and they have gone on to dissect the regulatory elements involved in their expression. They have also generated mice that make excess metallothionein or cannot make specific metallothionein proteins as a means of exploring their function in animals.
Palmiter is perhaps best known for his pioneering studies making transgenic mice in a transcontinental collaboration with Dr. Ralph Brinster at the University of Pennsylvania. They were the first to introduce functional genes into the genome of mice, rabbits, sheep and pigs. Animals carrying foreign genes are called transgenic. They created the so-called 'super mouse' that grew larger than normal as a consequence of adding hybrid gene to the genome of the mouse. Those mice carried a growth hormone gene that was controlled by the regulatory elements of a metallothionein gene. During their fifteen-year collaboration they produced thousands of transgenic mice in the process of examining many different biological questions. They used transgenic mice to discover the DNA sequences important for restriction of gene expression to specific cell types. They also used this technique to study genes that promote cell transformation and cancer.
Palmiter's group has used gene knockout techniques to inactive genes responsible for synthesis of chemical transmitters that are used by the nervous system. This allows them to study the role of these messengers in development and function of the nervous system. Using this approach they have learned that noradrenaline is essential for normal maternal behavior and defense against cold stress. Mice that cannot make neuropeptide Y eat and grow normally but they are alcoholic and prone to epileptic seizures. Their group has also learned that zinc is used as a chemical transmitter in the brain and that it prevents excessive excitability of the CNS. Mice that cannot make dopamine are hypoactive. In addition they are not motivated to eat or drink. However, they can be kept alive with pharmacological delivery of L-DOPA or viral gene therapy with vectors that restore L-DOPA synthesis.
Most recently, his group has begun turning their attention to better understanding of Parkinson's disease (PD). PD is characterized by a gradual loss of neurons that produce dopamine. While the mice that cannot make dopamine represent an extreme form of PD, the neurons are intact in that model. Current ideas suggest that disruption of mitochondrial function (deficient ATP production and/or excessive production of oxygen radicals) and the accumulation of damaged proteins may lead to the demise of dopaminergic neurons. Genetic models that mimic these processes are being developed.
Palmiter was born in Poughkeepsie, NY on April 5, 1942. He earned his BA in Zoology at Duke University in 1964 and a PhD from Stanford University in Biological Sciences in 1968. He has been at the University of Washington since 1974 and was appointed as Investigator of the Howard Hughes Medical Institute in 1976. The National Institutes of Health and the Michael J. Fox Foundation have also funded his research. He has been a member of the National Academy of Sciences since 1984.